Racial differences in gene-specific DNA methylation levels are present at birth
- PMID: 21308978
- PMCID: PMC3429933
- DOI: 10.1002/bdra.20770
Racial differences in gene-specific DNA methylation levels are present at birth
Abstract
Background: DNA methylation patterns differ among children and adults and play an unambiguous role in several disease processes, particularly cancers. The origin of these differences is inadequately understood, and this is a question of specific relevance to childhood and adult cancer.
Methods: DNA methylation levels at 26,485 autosomal CpGs were assayed in 201 newborns (107 African American and 94 Caucasian). Nonparametric analyses were performed to examine the relation between these methylation levels and maternal parity, maternal age, newborn gestational age, newborn gender, and newborn race. To identify the possible influences of confounding, stratification was performed by a second and third variable. For genes containing CpGs with significant differences in DNA methylation levels between races, analyses were performed to identify highly represented gene ontological terms and functional pathways.
Results: 13.7% (3623) of the autosomal CpGs exhibited significantly different levels of DNA methylation between African Americans and Caucasians; 2% of autosomal CpGs had significantly different DNA methylation levels between male and female newborns. Cancer pathways, including four (pancreatic, prostate, bladder, and melanoma) with substantial differences in incidence between the races, were highly represented among the genes containing significant race-divergent CpGs.
Conclusions: At birth, there are significantly different DNA methylation levels between African Americans and Caucasians at a subset of CpG dinucleotides. It is possible that some of the epigenetic precursors to cancer exist at birth and that these differences partially explain the different incidence rates of specific cancers between the races.
Copyright © 2011 Wiley-Liss, Inc.
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References
-
- Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, Bonnen PE, de Bakker PI, Deloukas P, Gabriel SB, Gwilliam R, Hunt S, Inouye M, Jia X, Palotie A, Parkin M, Whittaker P, Chang K, Hawes A, Lewis LR, Ren Y, Wheeler D, Muzny DM, Barnes C, Darvishi K, Hurles M, Korn JM, Kristiansson K, Lee C, McCarrol SA, Nemesh J, Keinan A, Montgomery SB, Pollack S, Price AL, Soranzo N, Gonzaga-Jauregui C, Anttila V, Brodeur W, Daly MJ, Leslie S, McVean G, Moutsianas L, Nguyen H, Zhang Q, Ghori MJ, McGinnis R, McLaren W, Takeuchi F, Grossman SR, Shlyakhter I, Hostetter EB, Sabeti PC, Adebamowo CA, Foster MW, Gordon DR, Licinio J, Manca MC, Marshall PA, Matsuda I, Ngare D, Wang VO, Reddy D, Rotimi CN, Royal CD, Sharp RR, Zeng C, Brooks LD, McEwen JE. Integrating common and rare genetic variation in diverse human populations. Nature. 2010;467(7311):52–58. - PMC - PubMed
-
- Ashktorab H, Smoot DT, Carethers JM, Rahmanian M, Kittles R, Vosganian G, Doura M, Nidhiry E, Naab T, Momen B, Shakhani S, Giardiello FM. High incidence of microsatellite instability in colorectal cancer from African Americans. Clin Cancer Res. 2003;9(3):1112–1117. - PubMed
-
- Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, Nelson HH, Karagas MR, Padbury JF, Bueno R, Sugarbaker DJ, Yeh RF, Wiencke JK, Kelsey KT. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009;5(8):e1000602. - PMC - PubMed
-
- Dalgaard P. [R] Kruskal-Wallis stratified rank sum test. 2005
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